This bio-medical research program is designed to elucidate relationships of altered energy metabolism on central nervous system function with age. Using the rat as a mammalian model system of aging, the proposed studies involve combined physiological, biochemical and biophysical approaches, e.g., standardized bioassay of brain substrates in conjunction with in situ atraumatic optical monitoring of C.N.S. changes in the redox state of cytochrome c oxidase, hemoglobin saturation, and blood volume. The latter methodology permits "real time" measurements of intracellular metabolic events simultaneous with cerebrovascular alterations. The project will focus on determining physiological, pharmacological, and pathobiological factors responsible for changes in C.N.S. hemodynamic and metabolic adaptive responsiveness with age. Stress displacement will be used as a means for revealing otherwise obscure age-associated functional, metabolic and cerebrovascular impairments. Sympathomimetic agonists and antagonists will be tested to explore modification of C.N.S. metabolism and vascular reactivity with age. Models of surgically induced stroke and shock have been constructed in young and aged animals. These procedures have been specifically designed to allow for assessment of pharmacotherapeutic regimens.